Give what you can and keep what you need!

Abstract

EMBO J 32 18, 2439–2453 doi:; DOI: 10.1038/emboj.2013.170; published online July 30 2013

During cell division, peroxisomes are inherited to daughter cells but some are retained in the mother cells. Our knowledge on how peroxisome inheritance and retention is balanced and how this is regulated for each individual organelle remains incompletely understood. The new findings by Knoblach et al (2013) published in this issue of The EMBO Journal demonstrate that Inp1p functions as a bridging protein to connect ER-resident Pex3p and peroxisomal Pex3p, which anchors peroxisomes to the cortical ER for organelle retention in the mother cell. Asymmetric peroxisome division generates peroxisomes, which lack Inp1p but contain Inp2p instead, and only these peroxisomes are primed for myosin-driven transport to daughter cells.

Figure 1

Peroxisome retention and inheritance (A) free peroxisomes in the mother cell (stage I) are anchored to cortical ER by a tethering complex consisting of two molecules Pex3p, one located at the ER and the other associated with the peroxisomal membrane and Inp1p, which connects the ER-bound and peroxisome-bound Pex3p (stage II). Accordingly, Inp1p contains two Pex3p-binding domains, allowing the protein to function as a bridge between the two Pex3p-containing organelles. Peroxisomes elongate and divide, and Inp2p is loaded onto peroxisomes with an asymmetric distribution (stage III). The peroxisomal population that lacks Inp2p is anchored to the cortical ER, whereas the population of cytosolic peroxisomes containing Inp2p is destined for the transport to the bud (stage IV). To this end, Inp2p interacts with Myo2p and thus triggers the movement of the peroxisome along actin cables to the bud. The process is completed when the peroxisome is released from Myo2p in the bud (stage I). In wild-type cells, the described retention and inheritance process leads to an equal distribution of peroxisomes between mother cell. The described molecular mechanism results in a regulated balance of retention and inheritance of peroxisomes, ensuring that both the mother cell and the newly formed bud gain their share of peroxisomes. (B) However, when the endogenous Pex3p is replaced by a Pex3p-mutant (Pex3p–V81E), which lost its strong binding capacity to Inp1p, peroxisomes are not anchored to the cortical ER anymore, with the consequence that during cells’ division the entire organelle population is transported to the bud and peroxisomes are not retained in the mother cell.